The overall objective of this research is to elucidate the effects of protein and zinc deficiencies, alone and in combination, on the efficacy of BCG vaccination. Results to date indicate that protein- and zinc-malnourished BCG-vaccinated quinea pigs have impaired cell-mediated immune function as measured by absence of delayed hypersensitivity to tuberculin, reduced phytohemagglutinin-stimulated lymphocyte blastogenesis in vitro, and increased numbers of viable BCG in the tissues. The implcation that these animals are not protected by BCG vaccination will be tested by challenging vaccinated guinea pigs maintained on adequate and deficient diets with an aerosol containing attenuated M. tuberculosis, H37Ra. Protection against respiratory infection will be assessed by enumerating the in vivo growth of H37Ra in the lungs, spleen and lymph nodes of infected animals. The effect of increasing the vaccine dose, vaccinating 2-3 weeks prior to initiation of the experimental diets and giving a booster injection of BCG will be assessed on the development of post-vaccination immune responses. The influence of humoral factors, especially antibodies, on BCG vaccine response in protein- and zinc-malnourished animals will be studied by measuring the general antibody-producing capability to a T-dependent antigen (sheep red blood cells) and monitoring the serum levels of antibodies to specific mycobacterial antigens using a sensitive enzyme-linked immunoassay.